The research proposed in this Pathways grant identifies and seeks to fill a current gap in knowledge regarding the relationship between aerobic exercise and cardiovascular fitness and functional and structural brain health in humans. The proposed human neuroimaging studies build upon a large body of existing animal research, and aim to extend this work to humans. The candidate is interested in establishing an independent research career in which she can study the effects of aerobic exercise and cardiovascular fitness on cognition and brain health in humans across the lifespan. The candidate's past and current research has included functional Magnetic Resonance Imaging (fMRI) studies of interactions between working memory and long-term memory and the role of the medial temporal lobes (including the hippocampus) and prefrontal cortex in working memory. The overall goal of this proposal is to prepare the candidate for a career as an independent scientist in translational cognitive neuroscience. Mentors include Dr. Chantal E. Stern, D.Phil., an expert in the cognitive neuroimaging of memory, Dr. Robert C. Wagenaar, Ph.D., a professor of exercise physiology and neurorehabilitation who is known for his work on movement disorders, Dr. Andrew E. Budson, M.D., an expert in cognitive and behavioral neurology, who is known for his work on cognitive dysfunction and memory dysfunction in Alzheimer's Disease, and Dr. Alice Cronin-Golomb, Ph.D. a professor of clinical psychology and an expert in the neuropsychology of aging. The goals of the research plan are to 1) establish a link between aerobic exercise, cardiovascular fitness, the functional neuroanatomy of hippocampal-dependent memory, and a neurotrophin, the Brain-Derived Neurotrophic Factor (BDNF) in humans using two memory tasks and fMRI (Specific Aim #1), 2) investigate whether a 12-week aerobic exercise intervention in healthy young and older sedentary adults is associated with an improvement in memory task performance, increased serum BDNF levels, and enhanced task-related hippocampal activity using fMRI and a pretest-posttest randomized control group design (Specific Aim #2), and 3) investigate whether the same aerobic exercise intervention in healthy young and older sedentary individuals results in increased volume in the hippocampus and/or hippocampal subfields, and cortical thickness in other brain areas using structural MRI and morphometric methods. The candidate will acquire essential training in exercise physiology and neurorehabilitation, geriatric neurology, clinical neuropsychological assessment, morphometric analyses of structural MRI images, and in clinical trial design. The project will enable the candidate to establish an externally funded research program in translational cognitive neuroscience. Aerobic exercise may be an effective and low-cost intervention resulting in healthy aging by promoting not only physical health, but also brain health. Regular moderate intensity aerobic exercise may have neuroprotective effects throughout the lifespan. PUBLIC HEALTH RELEVANCE: Regular moderate intensity aerobic exercise may be an effective and low-cost intervention for healthy aging by promoting not only physical health, but also brain health, and may have neuroprotective effects throughout the lifespan. These effects of exercise on the brain have been studied extensively in animal models, but not in humans. This set of studies aims to examine the relationship between aging, exercise, and the brain in healthy young and older individuals.